This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Parkinson's disease is a disabling disorder, causing progressive declines in motor, cognitive, and behavioral function. The underlying cause(s) of Parkinson disease remain(s) unknown. Recently, several investigators have observed that untreated Parkinson's patients have increased serum homocysteine (Hcy) levels and that dopaminergic therapies appear to further increase them. Elevated Hcy levels have been associated with increased Parkinson's severity. Elevated Hcy levels are also commonly associated with folate deficiency. In Parkinson's patients, the reasons for elevated Hcy levels have not been identified;several small clinical trials and epidemiological studies have failed to demonstrate an effect of oral folate on Hcy levels or in reducing risk of Parkinson's, suggesting that hyperhomocysteinemia in Parkinson's may not be due to decreased dietary intake of folate. Another possibility is the presence of autoantibodies to the folate receptor. In fact, these autoantibodies increase in frequency with advancing age much the way Parkinson's does. Therefore, we hypothesize that cerebral folate deficiency due to autoantibodies may contribute to the onset and progression of Parkinson's. Specific Aims: 1. To assess the prevalence of Folate receptor autoantibodies in Parkinson's patients compared with that in age-matched controls. 2.To assess the relationship between the presence of autoantibodies and plasma Hcy levels 3.To assess the relationship between Hcy and autoantibody levels and the clinical manifestations of Parkinson's. 4.To assess the relationship between Hcy and autoantibody levels and the rate of Parkinson's progression. 5.To assess the ability of orally administered L-methylfolate to lower Hcy levels and improve the signs and symptoms of Parkinson's.